The EU recognises that 6 out of 7 of the biggest risk factors for premature death are related to how we eat, drink and move. The major food and drink producers are aware of the fact that "healthy" options are high on the agenda of many consumers. However, obtaining proof of health benefits from the increased intake of so called "bioactive" food and drinks has not produced sufficient hard evidence to support health claims.
For commercial companies to invest large sums of money in nutrition and health research they must have a better chance of the investment achieving a return. Companies formulate products to increase their beneficial properties but there is a lack of tests available that have the sensitivity and specificity to measure health improvements. BioHealthClaim proposes such a test with high sensitivity and specificity based on validated urinary proteome analysis. We have demonstrated using this technology our ability to repeat the Eurolive study on a much smaller group made up of both male and female, old and young healthy volunteers over a shorter time scale (1).
The increase in chronic diseases in Europe, also as a result of increased life expectancy, requires guidance on dietary intake and consequently accurate labelling of food with specific health claims, which can only be accomplished through better testing techniques. The major objective of the BioHealthClaim project is to provide these better testing techniques. Based on the potential of the technology developed by Mosaiques therapeutics GmbH (MOT) we aim to provide a platform for assessing health claims of dietary products in an objective, unbiased way, based on disease-specific biomarkers. This data can then be used for improved product labelling and health claim promotion and marketing of products which will allow better consumer information, to allow informed choices in dietary habits and also for governments to provide accurate health advice. At present this market is fragmented and has no overall methodology for accessing health claims.
There are a number of multinational companies in the food and drink sector that are actively pursuing products that offer "healthy options" of existing or new products. However, to be able to market these with appropriate labelling they are required to make a health claim to the European Food Safety Authority (EFSA) or to the FDA in the USA. These companies include Barry Callebaut, Coca Cola, Mars, Nestlé, Pepsi Cola, Pom Wonderful, Unilever and Welch's Purple Grape juice, to name just a few of those that are MOTs subcontractor at Glasgow University (GU) has worked with. Barry Callebaut was allowed a rare EU health claim in 2013 for use on “Cocoa flavanols help maintain endothelium-dependent vasodilation, which contributes to normal blood flow”. This health claim was finally accepted after 8 years of research involving more than 20 human clinical studies.
One of the major problems with this type of nutritional research is that there are no adequate biomarkers of many of chronic diseases that, at present, a dietary intervention study can measurably change. MOT has identified a number of urinary biomarkers of diseases and developed high-dimensional classifiers employing these biomarkers, enabling assessing these diseases, including diabetes (6-7), coronary artery disease (CAD)(5) and chronic kidney disease (CKD) (3-4), the three major nutritionally relevant diseases.
At present there are no accepted tests for CAD or CKD in nutritional health claims, only measurements that show a maintenance of physiological effect, blood pressure, LDL cholesterol etc. are accepted. The clinical biomarkers for CAD and CKD are innovative tests that could revolutionise the health claims procedure and will increase competitiveness and sustainability by accessing this new market.
These biomarkers were developed for clinical diagnostic purposes and to inform clinicians on treatment progression. They have high specificity and sensitivity for each disease, were tested in several clinical studies and are now employed in a placebo-controlled randomized clinical intervention trial (PRIORITY) and were directly linked to the disease molecular pathophysiology. As demonstrated in several studies, the biomarkers enable detection of the onset of a disease before symptoms develop. While these biomarkers were designed for the clinical market there is a clear opportunity to harness this diagnostic testing to evaluate the impact that bioactive foods, drinks or specific ingredients can have on human health. A pilot study employing these biomarkers has shown that the intake of 20 ml of olive oil per day can have a statistically significant beneficial effect on the biomarker of CAD but not the biomarkers of diabetes or CKD after only 6 weeks and was not influenced by the phenolic content of the oil (1). In another pilot study the significant positive impact of a bespoke polyphenol rich drink was demonstrated (2).
The urinary biomarkers are analysed by Capillary Electrophoresis-Mass Spectrometry (CE-MS) technology developed by MOT, which are in use for clinical purposes, for the evaluation of health promoting nutritional and nutraceutical products. Urine is the body fluid of choice for analysis, for a number of reasons (8), and is prepared under mild conditions preserving the peptides / proteins of interest for subsequent CE-MS analysis. In capillary electrophoresis the peptides / proteins are separated according to their charge and mass. CE based separation has advantages in comparison to other methods, e.g. LC, especially in improved reproducibility and resolution (9-10). The obtained data comprise the information for abundance, retention time and mass for each peptide detected, which is then compared to previously validated biomarkers of disease for assessment (11). Changes in the biomarker scoring for each disease state due to changes in dietary intake can then be measured.
By providing a validated method for testing the efficacy of their products, the nutritional and nutraceutical industries benefits from enhanced product labelling and promotion. It would also allow governments to provide accurate informed dietary health advice and allow consumers to make informed dietary choices.
The functional food market is another market where we expect there to be interest in our biomarkers testing. Functional foods are those that have added ingredients or an increased level of the alleged active ingredient that provides a health benefit beyond basic nutrition. There is a blurred line between functional foods and nutraceuticals, depending on which definition is used. Our biomarker methodology is ideally suited to this type of food testing for health improvements and this sector would also be targeted for use of our product.
In conclusion the ambition of the BioHealthClaim is to provide a new service to the food and drink sector as well as the nutraceutical industry to provide health claim evidence for their products. While this will boost the use of the clinical biomarkers developed by MOT and increase the sustainability and competitiveness of MOT it will also provide a range of benefits to a number of sectors. The food and drink sector will have a new more sensitive and selective method to assess the health benefits of their products. It will also allow testing of specific ingredients within formulations of products, such as a specific polyphenol being the prime health promoter in cocoa, and could therefore drive the pace of developments in this market. This could lead to better labelling of so called health foods and restrict unsubstantiated general claims. More accurate food labelling will also lead to a better informed consumer, able to make knowledge based choices. This technology could provide a means of helping the population make healthier nutritional choices leading to a longer healthier life and a reduced burden on government health care sectors.
BioHealthClaim builds on existing, fruitful collaborations between MOT and the subcontractor GU. It provides a unique opportunity to enhance and expand their activities on the establishment of a new methodology for the assessment of health foods in disease prevention and to provide the consumer with validated healthy choices with better food labeling through sharing their expertise and complementary skills. MOT and the subcontractor GU have long established collaborations, also evident from joint publications. Both played leading roles in the initial development of the use of biomarkers in nutritional studies. Both are experienced in the design of clinical studies and data management, and have leading roles in large scale studies on biomarker research. MOT has selected GU participating in the BioHealthClaim project in order to provide the required capacities to cover all the expertise fields faced by the project, thus ensuring the scientific excellence to fulfill the objectives initially planned.
1. S. Silva et al., The American Journal of Clinical Nutrition, (January 1, 2015, 2015). 2. W. Mullen et al., J Agr Food Chem 58, 2586 (Feb 24, 2010). 3. J. Siwy et al., Nephrol Dial Transpl 29, 1563 (Aug, 2014). 4. A. Argiles et al., Plos One 8, e62837 (2013). 5. C. Delles et al., J Hypertens 28, 2316 (Nov, 2010). 6. D. M. Maahs et al., Plos One 5, (Sep 28, 2010). 7. J. K. Snell-Bergeon et al., Diabetes Technol The 11, 1 (Jan, 2009). 8. A. Albalat et al., Expert Rev Proteomic 8, 615 (Oct, 2011). 9. W. Mullen et al., Electrophoresis 33, 567 (Feb, 2012). 10. J. Klein et al., Electrophoresis, (Oct 8, 2013). 11. H. Mischak et al., Proteom. Clin. Appl. 5, 9 (Feb, 2011)